Bilateral asymmetry in C. elegans can arise from left-right asymmetric cell lineages. The single left-right unpaired MI neuron descends from the right side of an otherwise left-right symmetric cell lineage: the homologous cell on the left side becomes the
e3D epithelial cell.
To identify the mechanisms that generate the MI-
e3D asymmetry, we screened for mutants in which the MI-
e3D asymmetry is lost. We isolated 16 mutations in 7 genes that transform MI into an
e3D-like cell, thereby generating symmetry in a normally left-right asymmetric cell lineage. We previously showed that the establishment of the MI-
e3D asymmetry requires left-right asymmetric expression of a CEH-36/NGN-1/HLH-2 transcriptional cascade (Nakano et al., Development, 2010). CEH-36 homeodomain protein is expressed in the MI grandmother cell but not in the
e3D grandmother cell. CEH-36 induces asymmetric expression of two bHLH proteins, NGN-1 and HLH-2, in the MI mother cell but not in the
e3D mother cell. We also showed that replication-coupled chromatin assembly is necessary for the MI-
e3D asymmetry (Nakano et al., Cell, 2011). Reduction of the activity of the CAF-1 complex, a histone chaperone that deposits histone H3-H4 onto replicating DNA, causes the loss of the MI-
e3D asymmetry.
Here we report that two mutations isolated from our screens,
n5342 and
n5351, are alleles of the gene
tlk-1. These mutant animals carry mutations in the
tlk-1 locus. Animals carrying a
tlk-1 deletion allele,
tm2395, also show the loss of the MI-
e3D asymmetry.
tlk-1 encodes an evolutionarily conserved serine-threonine kinase implicated in several chromatin-based processes, including transcriptional regulation, chromosome segregation and DNA damage responses. We are planning to test whether
tlk-1 is involved in CAF-1-mediated chromatin assembly or regulates expression of CEH-36, NGN-1 or HLH2. We hope that continued characterization of these genes will further reveal the mechanisms that establish bilateral asymmetry in the C. elegans nervous system.